The rational design of therapies to treat the consequences of pathological insults to the adult auditory nervous system requires a detailed knowledge of the neural substrates and their reactions to injury. At present, relatively little is understood about adaptive reorganization after injury. Our ultimate goal is to understand the neurobiology of changes in the adult brain after a fairly common injury to the auditory system, cochlear damage and sensorineural hearing loss. This requires detailed information, not now available, on the reaction of the central auditory pathways to the loss of cochlear nerve fibers and on their capacity for reorganization. In our pilot studies with the cat and chinchilla, cochlear damage, produced by acoustic trauma, initially destroyed cochlear nerve fibers projecting to specific zones in the cochlear nucleus (CN), the first brain structure to receive nerve fibers from the cochlea. In these deafferented zones, following a recovery period, there was a new growth of axons and endings and, thus, a reorganization of the synaptic connections of the CN neurons. We propose to study the adult chinchilla CN with microscopic and neurochemical methods to asses its capacity for plastic change. After lesioning the cochlea with acoustic trauma, we will use light and electron microscopic histological methods to determine the nature and measure the growth of the newly formed axons and their endings in the deafferented zones of the CN. To determine if new synapses are formed in the deafferented zones and which transmitters they may use, we will use immunohistochemical and biochemical methods to assess whether levels of synaptophysin, a presynaptic protein, as well as the storage, release and inactivation activities of several CN transmitters are altered in these areas. Finally, we will use electron microscopic methods to assess the synaptic reorganization of the neuropil and of specific types of neurons in the deafferented zones. We will measure the growth of new axons and synaptic endings, the relative proportions of different synaptic ending types, and the spatial pattern of synapses on specific types of neurons.